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Histopathological findings: severe epidermal hyperplasia with scattered apoptotic bodies (black arrows). Prominent capillaries on superficial dermis (white arrows). H&E stain, magnification ×200 (bar: 100 µm).
Source publication
Erythema multiforme in pigs is an acute, self-limiting disease characterized by red skin areas and often associated with anorexia, fever and respiratory problems. The cause of the disease remains unknown. In a recent study, animals of a commercial breeding herd in Greece were examined, and all animals were found seropositive for porcine reproductiv...
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Background
The existing detection methods for porcine circovirus type 2 (PCV2) specific antibodies in serum cannot determine the infection status, thus it is necessary to establish a method for detecting PCV2 antigen. The capsid protein (CAP) of PCV2, as a major structural protein that plays a significant role in viral replication and in inducing h...
Background
India recorded the first outbreak of African swine fever (ASF) in North-eastern region (NER) in the year 2020.
Aim
The current study was undertaken to investigate the transmission of African swine fever virus (ASFV) in the wild boars of Northeast India, particularly of Assam.
Material and Methods
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African swine fever virus (ASFV) poses a significant threat to the global pig industry, necessitating accurate and efficient diagnostic methods for its infection. Previous studies have often focused on a limited number of epitopes from a few proteins for detecting antibodies against ASFV. Therefore, the current study aimed to use multiple B-cell ep...
Citations
... To test the developed methods under field conditions, we have used them in the past for screening not only pigs generated for xenotransplantation and the corresponding non-human primate recipients [16,27], but also for a comprehensive screening of pig breeds such as the indigenous Greek black pigs [28], the Göttingen minipigs [29][30][31][32], the Aachen minipigs [33], the Mini LEWE minipigs [34], Göttingen minipigs with dippity pig syndrome [35], and Greek pigs with erythema multiforme [36]. Here, we screen German slaughterhouse pigs using PCR-based and immunological methods able to detect pig viruses and demonstrate again the robust functionality of these methods. ...
... PCV3 was discovered in 2016, it is common in domestic pigs and wild boars world-wide (for review see [66]). Since PCV3 was also found in healthy pigs, there is clear evidence that PCV3 is pathogenic since virus clones were able to induce porcine dermatitis and nephropathy syndrome (PDNS) in specified pathogen-free animals [67] PCV3 was also found in Greek pigs with erythema multiform [36] and in Göttingen minipigs with dippity pig syndrome [35]. In contrast to our findings in a German slaughterhouse, the prevalence of PCV2, PCV3, and PCV4 in slaughterhouses in one province in China was 56.8, 80, and 9.4%, respectively [68]. ...
Detection methods have been developed to prevent transmission of zoonotic or xenozoonotic porcine viruses after transplantation of pig organs or cells to the recipient (xenotransplantation). Eleven xenotransplantation-relevant viruses including porcine cytomegalovirus, a porcine roseolovirus (PCMV/PRV), porcine lymphotropic herpesviruses -1, -2, -3 (PLHV-1, 2, 3), porcine parvovirus (PPV), porcine circovirus 2, 3, 4 (PCV2, 3, 4), hepatitis E virus genotype 3 (HEV3), porcine endogenous retrovirus-C (PERV-C) and recombinant PERV-A/C have been selected. In the past, several pig breeds, minipigs and genetically modified pigs generated for xenotransplantation had been analyzed using these methods. Here, spleen, liver and blood samples from 10 German slaughterhouse pigs were screened using both, PCR-based and immunological assays. Five viruses: PCMV/PRV, PLHV-1, PLHV-3 and PERV-C were found in all animals, and PCV3 in one animal. Some animals were latently infected with PCMV/PRV as only virus-specific antibodies were detected. Others were also PCR positive in spleen and/or liver, indicative of an ongoing infection. These results provide important information on the viruses that infect German slaughterhouse pigs and together with results of previous studies revealed that the methods and test strategies efficiently work under field conditions.
... Porcine astroviruses and porcine kobuviruses have been associated with neonatal piglet diarrhea (Qiu et al., 2022). Porcine lymphotropic herpesviruses (PLHVs) are widespread in pigs and, although no association between PLHVs and any pig diseases has been described Denner (2021); Halecker et al. (2022) suggested that they could be involved in the pathogenesis of erythema multiforme diagnosed in sows. Sus scrofa papillomavirus 1 (SsPV1), a member of Dyodeltapapillomavirus 1 species, has previously been described in domestic pigs and has been attributed to papillomatosis tumor Link et al., 2017). ...
... Despite the high prevalence of these viruses, until now, no association between PLHVs and any pig diseases had been described [37]. However, we recently described the finding of PLHV-3 in pigs with dippity pig syndrome (DPS) [16] and in Greek pigs with erythema multiforme [38]. Whether porcine lymphotropic herpesviruses, especially PLHV-3, pose a risk for xenotransplantation is unclear. ...
... PLHV was also not transmitted to baboons through the hearts of all eight genetically modified pigs used for orthotopic pig heart transplantation which were all positive for PLHV-3 [10]. As mentioned, PLHV-3 was also found in pigs suffering from DPS [16] and from erythema multiforme [38]. However, it remains unclear whether the virus is involved in the corresponding pathogenesis. ...
The successful advancement of xenotransplantation has led to the development of highly sensitive detection systems for the screening of potentially zoonotic viruses in donor pigs and preventing their transmission to the recipient. To validate these methods, genetically modified pigs generated for xenotransplantation, numerous minipigs and other pig breeds have been tested, thereby increasing our knowledge concerning the pig virome and the distribution of pig viruses. Of particular importance are the porcine cytomegalovirus, a porcine roseolovirus (PCMV/PRV) and the hepatitis E virus genotype 3 (HEV3). PCMV/PRV has been shown to reduce the survival time of pig transplants in non-human primates and was also transmitted in the first pig heart transplantation to a human patient. The main aim of this study was to determine the sensitivities of our methods to detect PCMV/PRV, HEV3, porcine lymphotropic herpesvirus-1 (PLHV-1), PLHV-2, PLHV-3, porcine circovirus 2 (PCV2), PCV3, PCV4 and porcine parvovirus 1 (PPV1) and to apply the methods to screen indigenous Greek black pigs. The high number of viruses found in these animals allowed for the evaluation of numerous detection methods. Since porcine endogenous retroviruses (PERVs) type A and B are integrated in the genome of all pigs, but PERV-C is not, the animals were screened for PERV-C and PERV-A/C. Our detection methods were sensitive and detected PCMV/PRV, PLHV-1, PLHV-1, PLHV-3, PVC3 and PERV-C in most animals. PPV1, HEV3, PCV4 and PERV-A/C were not detected. These data are of great interest since the animals are healthy and resistant to diseases.
... An entire detection system including sample generation, sample preparation, sample origin, time of sampling as well as negative and positive controls is important [12,13]. Using these detection systems, different minipigs such as the Auckland Island pigs [14,15], the Göttingen minipigs [16][17][18][19][20][21][22], Göttingen minipigs with dippity pig syndrome (DPS) [23], the Aachen minipigs [24] and the Mini LEWE pigs [25] as well as genetically modified pigs generated for xenotransplantation [10,[26][27][28][29][30][31], Greek pigs with erythema multiforme [32] and wild boars [33,34] were analyzed. ...
... Despite the high prevalence of these viruses, until now, no association between PLHVs and any pig diseases had been described [55]. However, we recently described the finding of PLHV-3 in pigs with dippity pig syndrome [23] and Greek pigs with erythema multiforme [32]. Whether porcine lymphotropic herpesviruses, especially PLHV-3, pose a risk for xenotransplantation, is unclear. ...
... PLHV was also not transmitted to baboons through the hearts of eight out of eight genetically modified pigs used for orthotopic pig heart transplantation which were all positive for PLHV-3 [10]. As mentioned, PLHV-3 was also found in pigs suffering from dippity pig syndrome (DPS) [23] and from erythema multiforme [32]. However, it remains unclear whether the virus is involved in the corresponding pathogenesis. ...
The successful advancement of xenotransplantation has led to the development of highly sensitive detection systems for the screening for potentially zoonotic viruses in donor pigs and preventing their transmission to the recipient. To validate these methods, genetically modified pigs generated for xenotransplantation, numerous minipig and other pig breeds have been tested, thereby increasing our knowledge concerning the pig virome and the distribution of pig viruses. Of particular importance are the porcine cytomegalovirus, a porcine roseolovirus (PCMV/PRV) and the hepatitis E virus genotype 3 (HEV3). PCMV/PRV has been shown to reduce the survival time of pig transplants in non-human primates and was also transmitted in the first pig heart transplantation to a human patient. Here, we determined the sensitivities of our methods to detect PCMV/PRV, HEV3, porcine lymphotropic herpesvirus - 1 (PLHV-1), PLHV-2, PLHV-3, porcine circovirus 2 (PCV2), PCV3, PCV4 and porcine parvovirus 1 (PPV1) efficiently and used the methods to screen indigenous Greek black pigs. Since porcine endogenous retroviruses (PERVs) of type A and B are integrated in the genome of all pigs, but PERV-C is not, the animals were screened for PERV-C and PERV-A/C. Our detection methods were sensitive and detected PCMV/PRV, PLHV-1, PLHV-1, PLHV-3, PVC3 and PERV-C in most animals. PPV1, HEV3, PCV4 and PERV-A/C were not detected. These data are of great interest since the animals are healthy and very resistant to diseases.
... Although pig and veterinary associations informed in detail about DPS [7-10], there are only very few scientific publications investigating cases of DPS [1][2][3][4][5][6]17] and these publications usually only include a short description of the disease. The literature describing erythema multiforme in commercial breeding pig herds is also rare [15,16]. Since DPS is found in minipigs bred for biomedical purposes [21,22], there is a great interest to analyze the cause of this disease in order to prevent it effectively [17]. ...
... These methods were also used to screen for viruses in GöMPs as these may serve as donor animals for islet cell transplantation into human diabetic recipients [23][24][25][26][27][28][29]32]. Other pig breeds such as the Aachen minipigs [33,34], the Mini-LEWE minipigs [35] and Greek pigs with erythema multiforme [16] were analyzed using these methods. The rationale for the selection of these so-called xenotransplantation-relevant porcine viruses [31] was among others the fact that HEV is indeed a well-known zoonotic virus [36] and PCMV/PRV has been shown to significantly reduce the survival time of pig xenotransplants in non-human primates [37][38][39]. ...
... glyceraldehyde-3-phosphate-dehydrogenase (pGAPDH) as internal control for each sample. Real-time PCR reactions were carried out with a qTOWER 3 G qPCR cycler (Analytik Jena, Jena, Germany) and the real-time PCR conditions for the detection of PCMV/PRV, PCV1, PCV4, PLHV-1 and PPV1 were applied as previously described [16]. An adapted PCR-time profile for PCV3 started with an activation step of 5 minutes at 95˚C, followed by 40 cycles comprising a denaturation step of 15 seconds at 95˚C, an annealing step of 60 seconds at 56˚C and an extension step of 30 seconds at 72˚C. ...
Dippity Pig Syndrome (DPS) is a well-known but rare complex of clinical signs affecting minipigs, which has not been thoroughly investigated yet. Clinically affected animals show acute appearance of red, exudating lesions across the spine. The lesions are painful, evidenced by arching of the back (dipping), and the onset of clinical signs is generally sudden. In order to understand the pathogenesis, histological and virological investigations were performed in affected and unaffected Göttingen Minipigs (GöMPs). The following DNA viruses were screened for using PCR-based methods: Porcine cytomegalovirus (PCMV), which is a porcine roseolovirus (PCMV/PRV), porcine lymphotropic herpesviruses (PLHV-1, PLHV-2, PLHV-3), porcine circoviruses (PCV1, PCV2, PCV3, PCV4), porcine parvovirus 1 (PPV1), and Torque Teno sus viruses (TTSuV1, TTSuV2). Screening was also performed for integrated porcine endogenous retroviruses (PERV-A, PERV-B, PERV-C) and recombinant PERV-A/C and their expression as well as for the RNA viruses hepatitis E virus (HEV) and SARS-CoV-2. Eight clinically affected and one unaffected GöMPs were analyzed. Additional unaffected minipigs had been analyzed in the past. The analyzed GöMPs contained PERV-A and PERV-B integrated in the genome, which are present in all pigs and PERV-C, which is present in most, but not all pigs. In one affected GöMPs recombinant PERV-A/C was detected in blood. In this animal a very high expression of PERV mRNA was observed. PCMV/PRV was found in three affected animals, PCV1 was found in three animals with DPS and in the unaffected minipig, and PCV3 was detected in two animals with DPS and in the unaffected minipig. Most importantly, in one animal only PLHV-3 was detected. It was found in the affected and unaffected skin, and in other organs. Unfortunately, PLHV-3 could not be studied in all other affected minipigs. None of the other viruses were detected and using electron microscopy, no virus particles were found in the affected skin. No porcine virus RNA with exception of PERV and astrovirus RNA were detected in the affected skin by next generation sequencing. This data identified some virus infections in GöMPs with DPS and assign a special role to PLHV-3. Since PCMV/PRV, PCV1, PCV3 and PLHV-3 were also found in unaffected animals, a multifactorial cause of DPS is suggested. However, elimination of the viruses from GöMPs may prevent DPS.
... To detect PCMV in our study, we used a modified realtime PCR originally developed by Mueller et al. [13], which was modified by us into a duplex real-time PCR. This PCR detects a conserved region in the polymerase gene of PCMV and was used by many laboratories, including ours [4,13,14,16,38,39]. To improve the diagnostic, an additional PCR would be useful, either detecting another sequence in the polymerase genes as described by us [17,40], or detecting a sequence in another gene, e.g., in the gene encoding the gB protein. ...
... When we used two recombinant fragments of the gB protein of PCMV/PRV, the N-terminal R1 and the C-terminal R2, we found that sera from most infected pigs recognized R2 [18]. Therefore, in later investigations, including this study, only R2 was used for testing [10,16,38]. ...
Background
Porcine cytomegalovirus (PCMV) is a porcine roseolovirus (PCMV/PRV) which is widely distributed in pigs. Transmission of PCMV/PRV in preclinical xenotransplantations was shown to significantly reduce the survival time of the pig transplants in non-human primates. PCMV/PRV was also transmitted in the first transplantation of a pig heart into a human patient. To analyze how PCMV/PRV could be introduced into pig breeds, especially considering cloned transgenic pigs, and subsequently spread in breeding facilities, we screened ovaries and derived materials which are used to perform somatic cell nuclear transfer (SCNT).
Methods
DNA was isolated from ovarian tissues, follicular fluids, oocytes with cumulus cells, denuded oocytes and parthenotes. A real-time PCR with PCMV/PRV-specific primers and a probe was performed to detect PCMV/PRV. Furthermore, a Western blot assay using a recombinant fragment of the gB protein of PCMV/PRV was performed to screen for virus-specific antibodies in the follicular fluids.
Results
PCMV/PRV was found by real-time PCR in ovarian tissues, in the follicular fluid and in oocytes. In parthenotes the virus could not be detected, most-likely due to the low amount of DNA used. By Western blot assay specific antibodies against PCMV/PRV were found in 19 of 20 analyzed follicular fluids.
Conclusion
PCMV/PRV was found in ovarian tissues, in the follicular fluids and also in denuded oocytes, indicating that the virus is present in the animals of which the oocytes were taken from. Despite several washing steps of the denuded oocytes, which are subsequently used for microinjection or SCNT, the virus could still be detected. Therefore, the virus could infect oocytes during genetic modifications or stay attached to the surface of the oocytes, potentially infecting SCNT recipient animals.
Background
As sequencing is becoming more broadly available, virus discovery continues. Small DNA viruses contribute to up to 60% of the overall virus load in pigs. Porcine circoviruses (PCVs) are small DNA viruses with a single‐stranded circular genome. They are common in pig breeds and have not been properly addressed for their potential risk in xenotransplantation. Whereas PCV1 is non‐pathogenic in pigs, PCV2 has been associated with various disease manifestations. Recently two new circoviruses have been described, PCV3 and PCV4. While PCV4 is currently present mainly in Asia, PCV3 is widely distributed, and has been identified in commercial pigs, wild boars, and pigs generated for xenotransplantation. In one case PCV3 was transmitted by pigs to baboons via heart transplantation. PCV3 pathogenicity in pigs was controversial initially, however, the virus was found to be associated with porcine dermatitis and nephropathy syndrome (PDNS), reproductive failure, and multisystemic inflammation. Inoculation studies with PCV3 infectious clones confirmed that PCV3 is pathogenic. Most importantly, recently discovered human circoviruses (CV) are closely related to PCV3.
Methods
Literature was evaluated and summarized. A dendrogram of existing circoviruses in pigs, humans, and other animal species was created and assessed at the species level.
Results
We found that human circoviruses can be divided into three species, human CV1, CV2, and CV3. Human CV2 and CV3 are closest to PCV3.
Conclusions
Circoviruses are ubiquitous. This communication should create awareness of PCV3 and the newly discovered human circoviruses, which may be a problem for blood transfusions and xenotransplantation in immune suppressed individuals.
